Heart failure (HF) is a complex syndrome resulting from the inability of the heart to pump blood sufficient to meet the body's needs. Heart failure is a progressive disease most common in the elderly and usually caused by other diseases/conditions that gradually damage the heart such as coronary heart disease, damaged heart valves, external pressure around the heart, and cardiac muscle disease. The kidneys play an important role in compensating for the heart's inability to pump blood. Normally, healthy kidneys are responsible for various functions such as: removal of fluid and wastes, maintenance of blood pressure, maintenance of acid-base balance, stimulation of red cell production (via the release of erythropoetin), and promotion of calcium absorption. In heart failure patients, the kidneys compensate for inadequate cardiac output by increasing the volume of circulating blood (by decreasing urine output), and maintaining blood pressure. In the short term these compensatory mechanisms serve to increase cardiac performance. However in the long term they become maladaptive and lead to fluid overload in the patient, which is manifested as excess lung fluid (pulmonary edema) and dyspnea.
Thus chronic heart failure leads to a vicious cycle (termed the cardiorenal syndrome), where heart failure advances renal disease, which in turn further worsens heart failure. Chronic heart failure worsens renal diseases by several mechanisms. A reduction in the cardiac output reduces the blood flow to the kidneys and hampers the ability of the kidneys to filter wastes and remove fluid. Renal ischemia resulting from reduced oxygen availability activates the renin-angiotensin-aldosterone (RAAS) system, which causes salt and water retention and vasoconstriction (a reduction in caliber of blood vessels). Chronic activation of the RAAS system has toxic effects on the kidneys. Kidney disease in turn worsens heart failure by several mechanisms including, but not limited to, hypervolemia, increased sympathetic activity and pressure load, anemia, and inflammation. This coupled pathophysiology suggests why about 50% of patients with heart failure (i.e. 2.5 million) are estimated to have kidney disease and about 40% of patients with chronic kidney disease have heart failure. Patients suffering from failing kidneys have been reported to be the highest risk group for cardiovascular events.
Renal replacement therapy is required in patients with renal failure where the kidneys are unable to main normal functions. Renal replacement therapy is delivered using the processes of dialysis and ultrafiltration to remove the waste products, and extra fluid that accumulates when kidneys stop functioning. Renal replacement therapy also helps normalize many of the chemical imbalances that accompany kidney failure. Dialysis is the transfer of small solutes across a semi permeable membrane from the side of higher concentration (blood side) to the side of lower concentration. Ultrafiltration is the removal of water and small-to-medium solutes (by convection) through the application of a hydrostatic pressure across a semi-permeable membrane. The term “clearance” is used to describe the complete removal of a substance from a specific volume of blood per unit time.
Extracorporeal renal replacement therapy (ERRT) is the most common type of renal therapy where blood is circulated outside the body through a filter called a hemodialyzer. Most patients need three or four therapy sessions per week, each lasting two to four hours. During dialysis small solutes are removed by diffusion, the concentration of solutes in the plasma decreases, and clearance is obtained. Ultrafiltration can be combined with dialysis to remove both fluid and small solutes from the blood plasma during ERRT. It is important to measure the amount of clearance and fluid removed during dialysis. Hemofiltration is the combination of ultrafiltration and fluid replacement.
Blood circulation for ERRT is provided using an electromechanical system that comprises a blood pump to move blood from the patient's artery/vein through an extracorporeal blood circuit containing tubes and a hemofilter or hemodialyzer. For hemodialysis an ionic solution called the dialysate is pumped through the dialyzer in a direction counter-current to blood flow and on the opposite side of the semi permeable membrane. Because the dialysate does not contain wastes (such as urea and creatinine) that are present in blood, the chemical concentration gradient of these substances across the semi-permeable membrane drives diffusion in to the dialysate stream, which is discarded. The dialysis instrument also controls the transmembrane pressure to ensure that the required fluid is removed by ultrafiltration during the therapy. If necessary, small amounts of fluids and medications may be injected into blood returning to the patient. During ultrafiltration therapy, since dialysis is not required a dialysate solution is not needed, and blood is passed through a hemofilter across which a fluid similar to plasma is filtered. Depending on the permeability of the membrane, a filtrate similar to plasma is collected through a filtrate tube and temporarily stored in a filtrate bag. Through convection, the filtered fluid also drags solutes of different sizes and molecular weights across the membrane.
Due to the cardiorenal syndrome, patients with advanced heart failure are often fluid overloaded. Because patients still retain kidney function, they are treated using a class of drugs called diuretics that promote urine discharge. However diuretics are known to have adverse events. Sometimes patients may be admitted to the hospital for decompensated heart failure and require therapies such as ultrafiltration for immediate fluid removal. Ultrafiltration, which is typically used for renal therapies, is thus being increasingly used for managing fluid removal from heart failure patients. The advantages of ultrafiltration over diuretics are that the rate of fluid output can be easily adjusted, and the process removes both sodium and water, which is important to maintain fluid balance.
An increasing number of heart failure patients are also implanted with cardiac rhythm management (CRM) devices that treat their heart failure condition. CRM devices such as pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices are used to treat electrical conduction disorders of the heart. Also CRM devices are equipped with a variety of implanted sensors that monitor the heart and provide for the measurement of several physiological parameters, including, but not limited to, electrical cardiac activity, heart rate, heart rate variability, autonomic balance, patient activity, temperature, thoracic fluid, and respiration. These sensors are advantageous over external sensors because they can make measurements automatically in the ambulatory patient while minimizing patient discomfort and the need for patient compliance. About 60% of cardiovascular deaths in patients undergoing renal therapy are thought to be due to sudden cardiac death making patients undergoing end-stage renal therapies, such as dialysis, potential candidates for CRM devices.
It is beneficial to measure the physiological characteristics of the body during renal replacement therapy, or ultrafiltration for heart failure. Present methods of renal replacement therapy do not provide a means whereby implanted sensor measurements may be taken. For example during renal replacement or ultrafiltration therapies, an excess removal of fluid from the patient can lead to a rapid reduction in blood pressure (hypotension). This occurs due to the inability of the body to increase total peripheral resistance in the face of decreasing cardiac output. Thus a method is required to continuously monitor the fluid status and the autonomic function of the patient and control ultrafiltration rate in order to ensure that the patient reaches his/her dry weight without hypotensive episodes. Sensors present in implanted CRM devices can be used to monitor the patient during ERRT and/or ultrafiltration therapies and control therapy. Autonomic balance can be measured from heart rate variability using cardiac electrical activity measured from CRM devices, which could be used to detect increasing sympathetic tone prior to a hypotensive episode. Similarly the patient's thoracic fluid status measured using thoracic impedance in CRM devices may be useful in determining the fluid state of the patient. Also blood conductivity measurements from implanted CRM devices may be used for hematocrit determination, and dialysis clearance calculations of sodium, which is used as a surrogate for urea.
In addition to the above measurements that are made during ERRT or ultrafiltration, chronic implanted sensor data collected between treatments (e.g. autonomic balance, thoracic fluid status) in dialysis patients can be captured in the advanced patient management (APM) system and used by the caregiver to better manage the patient. For example chronic data from the CRM device and the APM system at home can be used to determine the rate of fluid build-up between dialysis sessions and alert the need for ERRT.
Presently the caregiver is required to analyze the data and provide predictive and post-event diagnosis based on the data. However, as the amount of data collected regarding a particular patient increases, it becomes more difficult for a caregiver to assimilate and provide a meaningful analysis of all of the data. In addition, it is difficult for a caregiver to identify trends and other information from particular patients and leverage this knowledge for the treatment of larger populations. Thus by integrating CRM sensors and the advanced patient management system with renal/ultrafiltration therapies, the patient can be more optimally managed.
Generally, during renal replacement therapy, the physiological characteristics of a patient are measured externally. Such externally measured physiological characteristics are not as beneficial as physiological characteristics that are measured internally by an implanted device. There is a need for a process whereby the local measurements of the physiological characteristics of a patient can be used in renal therapy and in the health management of patients with cardiac and renal disease.